Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 48, Pages 20417-20422Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910350106
Keywords
synthetic prions; stability; amyloid; neurodegeneration; conformation
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Funding
- University of California, San Francisco
- G. Harold and Leila Y. Mathers Foundation
- National Institutes of Health [NS064173, AG02132, AG10770, AG021601]
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institutes of Health Pathway to Independence
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Prions are infectious proteins that encipher biological information within their conformations; variations in these conformations dictate different prion strains. Toward elucidating the molecular language of prion protein (PrP) conformations, we produced an array of recombinant PrP amyloids with varying conformational stabilities. In mice, the most stable amyloids produced the most stable prion strains that exhibited the longest incubation times, whereas more labile amyloids generated less stable strains and shorter incubation times. The direct relationship between stability and incubation time of prion strains suggests that labile prions are more fit, in that they accumulate more rapidly and thus kill the host faster. Although incubation times can be changed by altering the PrP expression level, PrP sequence, prion dose, or route of inoculation, we report here the ability to modify the incubation time predictably in mice by modulating the prion conformation.
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